Dopamine receptor stimulating activity of 5-hydroxy-6-methyl-2-aminotetralin derivatives.
The effects of 5-hydroxy-6-methyl-2-aminotetralins were evaluated for central and presynaptic peripheral dopaminergic activity. Di-ethyl (DK-121) and di-propyl (DK-118) derivatives inhibited the tachycardia produced by postganglionic cardioaccelerator nerve stimulation in the cat. This effect was blocked by haloperidol (100 micrograms/kg). DK-118 inhibited stimulation-induced contraction of the cat nictitating membrane. The pressor response produced by lumbar sympathetic chain stimulation in the isolated hindlimb of the cat was inhibited by DK-118 following intravenous administration. Reflex sympathetic activation produced by 30 sec bilateral carotid occlusion was also inhibited by DK-118 in the dog. Centrally, DK-118 caused contralateral circling behavior in rats who had unilateral lesions of the caudate nucleus. DK-118 did not effect DOPA levels in either the caudate nucleus or olfactory tubercle. In contrast, DK-121 decreased DOPA levels in the caudate nucleus but did not produce circling behavior in rats. Both compounds have weak emetic activity in dogs. These results suggest that DK-121 and DK-118 possess stimulant properties on dopaminergic receptors in the central and peripheral nervous system. However, DK-121 does not appear to stimulate postsynaptic dopamine receptors in the central nervous system.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009541:Nictitating Membrane / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D012399:Rotation; D013134:Spiperone / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014839:Vomiting / Q000139:chemically induced
D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013134:Spiperone; D004295:Dihydroxyphenylalanine; C031456:N,N-diethyl-5-hydroxy-6-methyl-2-aminotetralin; C031457:DK 118